A novel S1P1 modulator IMMH002 ameliorates psoriasis in multiple animal models.

ABSTRACT: Psoriasis is characterized by abnormal proliferation of keratinocytes, as well as infiltration of immune cells into the dermis and epidermis, causing itchy, scaly and erythematous plaques of skin. The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently. Here, we showed that IMMH002, a novel orally active S1P1 modulator, desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus. Using different psoriasis animal models, we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PASI score and pathological injure evaluation. Mechanistically, IMMH002 regulated CD3+ T lymphocytes re-distribution by inducing lymphocytes' homing, thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the thymus. Our results suggest that the novel S1P1 agonist, IMMH002, exert extraordinary capacity to rapidly modulate T lymphocytes distribution, representing a promising drug candidate for psoriasis treatment.

SUBMITTER: Jin J 

PROVIDER: S-EPMC7016294 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature